We shall continue to utilize intermediary metabolism in pregnancy as a model system for evaluating regulation in the fed and fasted state; and phosphorus metabolism during stimulation of secretary structures (particularly in pancreatic islets) to define molecular changes that characterize the transition from "rest" to "work". Studies in pregnancy will attempt to integrate contributions from multiple systems via kinetic analysis of alanine and glucose turnover in intact rats and metabolic characterization of isolated hepatocytes. Efforts to determine factors which influence perinatal and neonatal events will be extended in acute and longitudinal studies of pregnant humans. For investigations into phosphorus metabolism we shall employ pancreatic islets, freshly isolated by collagenase or specially conditioned following tissue culture. We shall continue to focus on: (a) the rapid transient efflux of orthophosphate from pancreatic islets which we have shown to constitute a new index of secretory stimulation (the "phosphate flush"); and b) the turnover of phosphatidylinositol. Efforts will be made to correlate the "phosphate flush" with flux of other ions such as calcium and to localize the "phosphate flush" and phosphatidylinositol metabolism in the sequence of stimulus-secretion coupling.